A Phase IIa randomized clinical trial of a respiratory syncytial virus and human metapneumovirus combination protein-based virus-like particle vaccine in adults 60–85 years of age

BACKGROUND: Respiratory syncytial virus (RSV)- and human metapneumovirus (hMPV)-associated lower respiratory tract disease (LRTD) contributes substantially to morbidity and mortality in older adults. IVX-A12 is an investigational combination vaccine comprised of two virus-like particles computationally designed to elicit immune responses against RSV and hMPV. In a Phase I randomized trial, IVX-A12 was well tolerated and elicited RSV- and hMPV-specific neutralizing antibody (nAb) responses in adults 60-75 years of age. METHODS: In this Phase IIa trial, healthy adults 60-85 years of age, including participants with stable, chronic conditions, were randomized 2:2:1 to receive one intramuscular dose of IVX-A12 (150 μg RSV/150 μg hMPV) with/without MF59® (oil-in-water adjuvant), or placebo (diluent), stratified by age group (60-69/70-85 years). Safety and immunogenicity were assessed through 365 days post-vaccination. RESULTS: Overall, 264 participants received IVX-A12 (n = 211) or placebo (n = 53). Solicited adverse reactions were mild-to-moderate in severity and were reported by 57.3% (n = 59/103), 75.0% (n = 81/108), and 37.7% (n = 20/53) of recipients of unadjuvanted IVX-A12, IVX-A12 + MF59®, and placebo, respectively. IVX-A12 induced increases in nAbs against RSV and hMPV. From baseline to Day 28, in IVX-A12 (±MF59®) recipients, nAbs against RSV A and B increased 5-6- and 3-4-fold, respectively, and nAbs against hMPV A and B both increased 2-3-fold. In IVX-A12 recipients, all except hMPV A nAbs remained above baseline levels at Day 365 and were higher than in placebo recipients. Addition of MF59® to IVX-A12 did not boost antibody responses nor increase their duration. Safety and immunogenicity were similar between the stratified age groups. CONCLUSIONS: IVX-A12 was well tolerated and induced RSV- and hMPV-specific antibody responses in adults 60-85 years of age. This trial demonstrated the feasibility of an RSV/hMPV combination vaccine.